1. Field of the Invention
The field of the invention relates to products enhanced with Morinda citrifolia, which may be administered to various animals, and more particularly to products for increasing CD8+ T cell activation in animals.
2. Background
A wide variety of different animal food formulations are commercially available. In the past, the nutrients or ingredients in these formulations were not typically designed to provide specific advantages to an animal if desired or needed. Animal food may be specifically designed to decrease the mortality rate of newborn stock animals. For example, the inherent developmental immaturity of the neonatal immune system of various stock animals represents a predisposing factor toward increased morbidity and mortality. Currently, the leading management strategy to diminish this morbidity and mortality, in dairy calves particularly, is through the ingestion of high quality colostrum to ensure adequate passive transfer (APT) of immunoglobulins. While APT is the aim of dairy calf raisers, it may be more easily accomplished on smaller, closed-herd dairies compared to larger, commercial, calf-raising farms.
In addition to immunoglobulins, high quality colostrum includes a full compliment of cytokines, growth factors, hormones and maternal leukocytes which play a central role in modulating neonatal, innate and adaptive immunity. Bovine colostrum is known to contain several cytokines, such as: IFN-γ, IL-1β, IL-1ra, IL-4, IL-6, IL-18, and TNF-α. Many of which can be found in their highest concentrations immediately after parturition, followed by a rapid decline in milk by five days postpartum. Various studies show that orally administered leukocytes and cytokines are readily absorbed and enter the circulation of the neonate.
Adaptive immunity requires a full repertoire of functional T cells, including CD4+ T helper cells, cytotoxic CD8+ T cells CTL, and γδ TCR+ subsets, in the defense against infections such as bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus (BVDV) and bovine respiratory syncytial virus (BRSV).
T helper cells express CD4+ and are composed of two major populations, T helper 1 (Th1) and T helper 2 (Th2) cells. These T cell subsets play an important role in coordinating the overall adaptive immune response by modulating the activities of many immune cells like macrophage-activation through secretion of cytokines such as IL-2 and IFN-γ. Effector CD4+ T cells help B cell responses and enhance CD8+ T cell development through activation of APC or secretion of cytokines, such as IL-2, IL-4, and IL-5. It is also well established that neonatal immunity favors a Th2 respond in the face of an invading pathogen. This bias against a Th1 response, during which pro-inflammatory cytokines are produced, reduces the possibility of alloimmune reactions between mother and fetus and helps protect against infection both in and ex utero. However, this Th2 biased cell response contributes to reduced vaccine responses and leaves the neonate more susceptible to microbial infection. Repeated antigen exposure over time, diminishing the Th2 cell polarization and/or increasing the Th1 cell polarization, accelerates the immune maturing process and potentially reduces allergy and atopy. The Th1 immune response, which can be detrimental during pregnancy, becomes increasingly important postpartum as it leads to the production of CD8+ CTL. These cells play a crucial role in the immune system with the ability to lyse infected cells.
γδ T-cells make up the smallest fraction of lymphocytes in the ileal mucosa and the largest fraction of PBMC in young calves. They have a wide range of functions, yet their role in immune surveillance and pathogen recognition is still poorly understood. There is evidence that γδ T cell function includes cytokine production and cytotoxic activity as well as immunomodulation and inflammatory response. Bovine γδ T-cells found in the spleen are more transcriptionally active than those located in the blood, which represent only a small fraction of circulating T lymphocytes.
The second leading management strategy in preventing neonatal losses is through the administration of antibiotics in milk replacer or by injection as a therapeutic use and/or prophylactic strategy. While this strategy is associated with reduced calf morbidity and mortality, this management technique is highly scrutinized for possibly speeding the development of antibiotic resistant pathogens and resulting in an un-organic product for consumers. In fact, as of 2003 the European Union had already banned the use of antibiotics and related drugs on livestock for the purpose of growth promotion. These restrictions are intended to preserve antibiotic effectiveness for human use. The World Health Organization has also recommended the cessation of use of growth-promoting antibiotics in production anaimals, and some anticipate that the United States will adopt similar restrictions in the near future.
As a result of consumer pressure, there has been a push for safe, natural, sustainable immunomodulators to enhance calf health and lower morbidity and mortality rates. Dietary supplements that can reduce industry dependency on antibiotics while increasing the likelihood of successful APT and improving immune function are being sought after. A wide range of immunomodulators including peptides, lipopolysaccharides, glycoproteins, lipid derivatives, proteins and substances isolated from microorganisms, have been identified and tested with varying degrees of success in the clinical setting.
Immunomodulators from botanical sources have received much notoriety for their immune enhancing effects, relatively low toxicity and bio-availability. One type of immunomodulator, polyunsaturated fatty acids, have been used to increase the energy density of animal diets and provide immune modulation. Optimal amounts of vitamins A and E have been shown to prompt immune responses similar to that of adult cattle. Calves from dams supplemented with mannan oligosaccharide tended to have greater serum rotavirus neutralizing titers and serum protein concentrations compared to control calves.
Morinda citrifolia (noni) fruit is a well recognized natural herbal product that reportedly has a broad range of antibacterial, anti-inflammatory, immune stimulatory and anti-tumor effects. The juice from the Morinda citrifolia fruit is considered to have an immune stimulatory effect mediated by a polysaccharide-rich substance, noni-precipitant (ppt).
Because most of the common medical treatments for the numerous medical problems discussed above can involve serious side effects, compositions containing natural products and nutraceuticals that would treat these diseases and syndromes with less contraindications and diminish the development of antibiotic resistance are highly desirable, not only to relieve suffering in the animals but also to improve the quality of human health.